Immune system is a defense system of human body. The main cells involving a immune response are T lymphocytes, B lymphocytes, and macrophages. Thoracic gland is the central immune organ for development and differentiation of T lymphocytes. Thymus factors (or hormones) secreted from thoracic gland are a series of essential substances necessary for development and differentiation of T lymphocytes, wherein Tβ4 is one of main thymus factors which structure and functions are relatively definite and known in the art. It is well known in the art that, Tβ4 was a polypeptide that firstly isolated by Goldstein, et al., from thymosin fraction 5 (TF5) extracted from bovine thoracic gland with 43 amino acids as shown in SEQ ID NO: 1, had a molecular weight of 4.963 KD, was free of disulfide bond and glycosylation (The Journal of Biological Chemistry, Vol. 257, No. 2, pp. 1000-1006, 1982, Chemical Characterization of Thymosin beta).
Tβ-4 is a protein expressed during the onset of heart disease in embryo, and is able to promote the migration of cardiac cells and influence the survival of these cells (Thymosin beta 4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, Vol. 432, Nov. 25, 2004). As indicated in the above document, said protein was able to prevent cells from death and to limit the formation of scare tissue in some extent after the onset of experimentally induced heart disease. Tβ-4 has been applied in clinical trials to promote the healing of skin wound. Researchers believe that Tβ-4 will be used in clinical trial phase for treatment of heart diseases in the near future.
As shown in one of the aforementioned researches on Tβ4 activity, Tβ4 improved the survival of embryonic and postnatal myocardial cells in tissue culture, and intra-peritoneal injection of said protein after deligation of coronary artery in rats could successfully stimulate heart repair and activate Akt survival kinase. These results indicated that T-β4 is a potential therapeutic target for acute coronary artery occlusion.
In the above documents, the researchers of State University of Texas also found a protein (i.e., Tβ4) produced during the development of heart could facilitate heart self-repairing after the onset of heart disease. The findings obtained in rat might finally result in the discovery of new methods for treatment of heart diseases and could change the treatment of heart diseases in the art.
New Tβ-4 derivatives having significantly higher activity than that of native Tβ-4 regarding repair of skin lesion, heart injury, etc. is unexpectedly found by the inventors of the present invention by taking tertiary structure analysis of the known Tβ-4, and genetic engineering modification of the N-terminal of the said protein.